Neurogenic bladder dysfunction is a common sequela following spinal cord injury (SCI). This condition includes urinary retention, overflow incontinence, urgency, reduced compliance, reflux, repetitive urinary tract infection (UTI), and, depending on the level of injury, autonomic dysreflexia [1, 2]. The anatomical and physiological similarities of pigs and humans provide a unique intermediate animal model for the study of neuro-urological conditions and offer a greater translational value than rodent models. The aim of this study was to explore and evaluate bladder function in the lower urinary tract (LUT) under normal conditions and following an experimental SCI.

Urodynamics was conducted in awake female Yucatan minipigs (n=5) prior to and at week 12 (W12) post T10/T11 severe contusion SCI. Prior to the injury, the pigs were acclimated to being suspended in a sling in a still position. In order to evaluate bladder function, a double lumen catheter with a solid pressure sensor on the tip was inserted into the urinary bladder through the urethra for filling the bladder with room temperature saline at a rate of 15ml/min and for measuring intra-vesical pressure. A second pressure sensor was placed in the rectum to measure intra-abdominal pressure. At the same time, two perineal surface electrodes were anatomically placed to record the EMG activity. A weight flowmeter was used to perform flowmetry at W12 post-injury. All sensors were connected to urodynamic equipment (Laborie Aquarius® XT, NH, USA). The bladder capacity, filling pressure, the amount of non-voiding contractions, voided volume, voiding efficiency, voiding pressure, flow rate and voiding duration were recorded. Pre/post-injury data were compared using paired t-test with 95% confidence intervals.

During the preinjury urodynamics, two different flow patterns were noted. Pattern one was characterized by a continuous bell-shaped curve with slight to moderate right asymmetry of the bell matching with very low EUS EMG activity. The second flow pattern showed similar characteristics except that during the last third of the contraction curve, a rhythmic intermittence of the flow occurred accompanied by a bursting-like firing of the EUS. Significant differences were found at W12 post-injury in the voided volume (201 ± 36.76 vs 54.22 ± 15.68; *p<0.05), bladder capacity (271.9 ± 41.82 vs 316.8 ± 44.56; *p<0.05), voiding efficiency (78.70 ± 11.16 vs 24.22 ± 6.513; **p<0.05) and flow rate of urine (24.02 ± 6.834 vs 5.648 ± 2.330; *p<0.05) compared to the pre-injured condition (Fig. 1). Moreover, it was found that urodynamic data were consistent with overflow incontinence, detrusor instability, detrusor underactivity and detrusor-sphincter dyssynergia type 1, 2, and 3.

Performing urodynamic studies under fully awake/ conditions yields similar characteristics that are present in all urinary cycle phases found in human studies for both non-injured and post-injury conditions. These similarities suggest the presence of comparable neural circuitries between pigs and human, including corresponding plasticity and pathologic processes after SCI. Note that the intermittency of the flow during the last third of the void in some pre-injury animals is an important difference with human void behavior that needs further investigation.

This result shows the minipig model is a reliable, translational, and clinically relevant model for the study of the LUT urodynamics under healthy and pathological conditions for therapeutic approaches.

Hamid, R., et al., Epidemiology and pathophysiology of neurogenic bladder after spinal cord injury. 2018. 36(10): p1517-27.
Savic, G., et al., Hospital readmissions in people with chronic spinal cord injury. 2000. 38(6): p. 371-377.